Study level

  • Honours

Faculty/School

Faculty of Health

School of Biomedical Sciences

Topic status

We're looking for students to study this topic.

Research centre

Supervisors

Dr Emma Bolderson
Position
Senior Research Fellow
Division / Faculty
Faculty of Health
Dr Joshua Burgess
Position
Visiting Fellow
Division / Faculty
Faculty of Health

Overview

The genome of our cells is damaged multiple times each day, by various factors including sunlight and reactive oxygen species. In order for the DNA damage response to be efficient, our cells utilise highly coordinated repair pathways that function accurately and rapidly throughout the damaged cell. Cells that do not repair DNA damage correctly will accumulate damage and display increased genomic instability, which is a key hallmark of cancer cells, promoting their survival and rapid growth. DNA repair pathways are increasingly a target for cancer therapy, including inhibitors of PARP1. In order for us to understand how DNA damage promotes tumourigenesis and also determine which tumours will respond to cancer therapies, it is essential for us to increase our understanding of DNA repair proteins and processes.

There are 17 Poly-ADP-ribose polymerases (PARPs) in human cells. These proteins function to modify other proteins to control diverse cellular processes such as DNA repair, cell growth and division, and cell death. Although the functions of some PARP proteins have been well characterised, little is known about several of them. My groups preliminary data suggest that several of the uncharacterised PARP proteins also respond to DNA damage and are likely to have a role within the DNA damage response. This research project will aim to characterise the role of PARP proteins in the DNA damage response and explore the potential implications for cancer therapy:

Aims and approaches

  1. To determine the response of previously uncharacterised PARP proteins to DNA damage. This aim will involve cell culture and immunofluorescence to determine the localisation of the PARP proteins following DNA damage.
  2. To determine the role of these PARP proteins in the DNA damage response. This aim will examine the effect of depleting PARP proteins using siRNA on DNA repair pathways via immunofluorescence, immunoblotting and DNA repair assays.
  3. To determine if modulation of the expression of these PARP proteins sensitises tumour cells to chemotherapeutic agents. This aim will involve drug sensitivity assays, including Cell Titre-glo, to measure the effect of depleting PARP proteins on the response of tumour cells to chemotherapeutic agents.

Outcome

This project will determine the roles of previously uncharacterised PARP proteins in DNA repair pathways. It will also show, similarly to the targeting of PARP1, whether these two proteins could be potential therapeutic targets for cancer treatment.

Keywords

Contact

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